Interleukin-2 With Sorafenib (BAY 43-9006) for Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2013 by Ohio State University Comprehensive Cancer Center.
Recruitment status was  Active, not recruiting
Information provided by (Responsible Party):
Paul Monk, Ohio State University Comprehensive Cancer Center Identifier:
First received: January 2, 2007
Last updated: June 19, 2013
Last verified: June 2013
The primary objective of this study will be to determine the toxicity and Maximum Tolerated Dose (MTD) of the combination of high dose aldesleukin and sorafenib in previously untreated patients with metastatic or unresectable clear cell renal carcinoma (RCC) and metastatic melanoma.

Condition Intervention Phase
Renal Cancer
Drug: Aldesleukin
Drug: Sorafenib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Bolus High Dose Interleukin-2 With Sorafenib (BAY 43-9006) in Patients With Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma

Resource links provided by NLM:

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose (MTD) and toxicity of high dose (HD) [ Time Frame: each cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the progression free survival. [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Evaluate in a preliminary manner the response rate. [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
  • Evaluate the activation of aldesleukin induced transcription factors (T cell PSTAT 5 activity) within patients immune cell subsets. [ Time Frame: Day 1 and Day 29 ] [ Designated as safety issue: No ]
  • Measure circulating levels of VEGF, VEGFR, IFN-γ, IL-5, and CD4+, CD25+, FoxP3 cell number (T regs). [ Time Frame: Day 1 and Day 29 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: December 2006
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aldekleukin Plus Dose Escalation Sorafenib
Patients will be admitted to a dedicated nursing unit for HD aldesleukin administration. Patients will receive bolus aldesleukin at a dose of 600,000 IU/Kg every eight hours on days 1-5 with a goal of 10-12 doses.
Drug: Aldesleukin
600,000 IU/kg every 8 hours on days 1-5 (week 1) to a maximum of 12 doses. Another cycle of HD aldesleukin will be started on day 15 (week 3).
Other Name: Proleukin
Drug: Sorafenib
To be initiated at a dose of 200 mg orally. Once it is determined that no further HD aldesleukin therapy will be given, sorafenib may be given daily at the FDA approved dose of 400 mg twice daily until there is lack of clinical benefit or intolerable side effects develop.
Other Name: Nexavar

Detailed Description:

Rationale: Previous research indicates that high dose aldesleukin produces tumor regression through upregulation of the patients' immune system. Research suggests that sorafenib directly targets tumors by inhibiting angiogenic activity with possibly some cytotoxicity. Angiogenic refers to the formation of new blood vessels that support tumor growth. Cytotoxicity is the measurement of a chemical's ability to damage or kill cancer cells. Researchers have hypothesized that the complementary ways aldesleukin and sorafenib work, and their non-overlapping toxicity profiles, may create a reasonable combination for the treatment of metastatic renal cell carcinoma and metastatic melanoma. The current Phase I study will evaluate toxicity in patients through assessing various dose levels of sorafenib in combination with aldesleukin.

Purpose: The primary objective is to determine the maximum tolerated dose and characterize the toxicity of high dose aldesleukin and sorafenib in patients with unresectable or metastatic clear cell renal carcinoma and metastatic melanoma. Secondary objectives include determining progression free survival in patients, evaluating in a preliminary manner response rates, and assessing other measurements in study participants.

Treatment: Study participants will be given bolus high dose aldesleukin and sorafenib. Aldesleukin will be provided through intravenous infusions on days 1 through 5. Each 5 day treatment is considered a cycle. The second cycle of aldesleukin will start on day 15. Two cycles are considered 1 course. All study participants will be given the same dose level of aldesleukin. No dose reductions will be permitted. Sorafenib will then be administered on day 29. Since this study will assess the maximum tolerated dose of sorafenib, some study participants will receive different amounts of this drug compared to others depending upon when each individual enrolls in the study. Each group of 3 to 6 study participants will receive a higher dose of sorafenib until the maximum tolerated dose is established. Imagining studies will be performed to determine response to treatment during week 12. If the patient has stable or responding disease, a second course will be administered on the same schedule. Patients without disease response will be given one additional course of aldesleukin past maximal response. When it is decided that no further aldesleukin will be provided to patients, sorafenib at the Food and Drug Administration approved dose may be continued until there is a lack of clinical benefit or intolerable side effects develop. Several tests and exams will be given throughout the study to closely monitor patients.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed evidence of metastatic/ unresectable clear cell renal carcinoma.
  • Patients must have metastatic melanoma with no brain metastases.
  • Patients must have measurable disease.
  • No prior systemic treatment (One prior systemic treatment is allowed for metastatic melanoma patients. Excluded prior therapies include prior high dose aldesleukin, sorafenib and DTIC/TMZ.)
  • Age ≥ 18 years or older

Exclusion Criteria:

  • Patients who are undergoing or have undergone surgery S weeks.
  • Patients who are pregnant (because of possible side effects on the fetus) Effective contraception will be discussed with each patient.
  • Patients with uveal melanoma.
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Please refer to this study by its identifier: NCT00418496

United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Principal Investigator: J. Paul Monk, M.D. Ohio State University
  More Information

Additional Information:
Responsible Party: Paul Monk, Principal Investigator, Ohio State University Comprehensive Cancer Center Identifier: NCT00418496     History of Changes
Other Study ID Numbers: OSU-06006  NCI-2011-03199 
Study First Received: January 2, 2007
Last Updated: June 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Kidney Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors processed this record on April 27, 2016